Spaceflight-Associated Brain White Matter Microstructural Changes and Intracranial Fluid Redistribution

Abstract

IMPORTANCE Spaceflight results in transient balance declines and brain morphologic changes; to our knowledge, the effect on brain white matter as measured by diffusion magnetic resonance imaging (dMRI), after correcting for extracellular fluid shifts, has not been examined. OBJECTIVE To map spaceflight-induced intracranial extracellular free water (FW) shifts and to evaluate changes in brain white matter diffusion measures in astronauts. DESIGN, SETTING AND PARTICIPANTS We performed retrospective, longitudinal analyses on dMRI data collected between 2010 and 2015. Of the 26 astronauts' dMRI scans released by the National Aeronautics and Space Administration Lifetime Surveillance of Astronaut Health, 15 had both preflight and postflight dMRI scans and were included in the final analyses. Data were analyzed between 2015 and 2018. INTERVENTIONS OR EXPOSURES Seven astronauts completed a space shuttle mission (Յ30 days) and 8 completed a long-duration International Space Station mission (Յ200 days). MAIN OUTCOMES AND MEASURES The dMRI scans were acquired for clinical monitoring; in this retrospective analysis, we analyzed brain FW and white matter diffusion metrics corrected for FW. We also obtained scores from computerized dynamic posturography tests of balance to assess brain-behavior associations. RESULTS Of the 15 astronauts included, the median (SD) age was 47.2 (1.5) years; 12 were men, and 3 were women. We found a significant, widespread increase in FW volume in the frontal, temporal, and occipital lobes from before spaceflight to after spaceflight. There was also a significant decrease in FW in the posterior aspect of the vertex. All FW changes were significant and ranged from approximately 2.5% to 4.0% across brain regions. We observed white matter changes in the right superior and inferior longitudinal fasciculi, the corticospinal tract, and cerebellar peduncles. All white matter changes were significant and ranged from approximately 0.75% to 1.25%. Spaceflight mission duration was associated with cerebellar white matter change, and white matter changes in the superior longitudinal fasciculus were associated with the balance changes seen in the astronauts from before spaceflight to after spaceflight. CONCLUSIONS AND RELEVANCE Free water redistribution with spaceflight likely reflects headward fluid shifts occurring in microgravity as well as an upward shift of the brain within the skull. White matter changes were of a greater magnitude than those typically seen during the same period with healthy aging. Future, prospective assessments are required to better understand the recovery time and behavioral consequences of these brain changes.

Prolonged Microgravity Affects Human Brain Structure and Function

“…This finding is consistent with the known role of the splenium of the corpus callosum in mediating fast visuomotor responses. 26 In astronauts, abnormal diffusion metrics involving multiple white matter tracts indicative of disrupted white matter connectivity have been identified postflight, 27 and in particular, a recent study found focally reduced fractional anisotropy within the right posterior thalamic radiation in astronauts postflight, a physiologic correlate to the local volume change we identify here. 28 Initially, we had hypothesized that ventricular enlargement postflight would correlate with the development of SANS; however, the 4 astronauts with ophthalmologic changes had a smaller change in %DVV than those without SANS (12.8% versus 6.5%, P = .02, n = 8 versus n = 4).…”

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

“…Another retrospective analysis of the brain MRI scans of 15 astronauts has also shown significant widespread spaceflightassociated free water increases at the base of the cerebellum and decrease along the posterior vertex which was reflecting disrupted white matter structural connectivity in the cerebellum, corticospinal tract and superior longitudinal fasciculus, among other regions after adjustment. 43 Unfortunately, some of the clinical and radiographic findings in SANS may not be unique to only LDSF because many of the astronauts thus far studied had previous SDSF and thus had no true pre-flight comparative data. In addition, some of the MRI findings (e.g., globe flattening) may be subtle and could easily be over-interpreted especially if the neuroradiologist is not masked to their flight status.…”

Effects of centrifugation and whole-body vibrations on blood–brain barrier permeability in mice

“…34 This is supported by transcriptomic and proteomic analysis of brain in mice models, 22,35,36 and more recently in humans by magnetic resonance imaging. 4,[37][38][39][40] As also proposed in the field of neurodegenerative disorders, an impairment of the BBB is suggested to induce or accelerate the processes of the memory impairments. 17 Our work participates to confirm the link between BBB dysfunction induced by gravity changes and putative memory impairments hypothesized recently, 15 yet this point should be investigated to understand its molecular basis.…”